Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus which is the etiological agent of infectious mononucleosis. EBV is also associated with a number of malignancies which includes Burkitt's lymphoma, Nasopharyngeal carcinoma, Oral Hairy leukoplakia, Hodgkin's lymphoma, Adult T-cell lymphomas and lymphoproliferative diseases in transplant and AIDS patients. In vitro, EBV infects and growth transforms B-lymphocytes so that they proliferate continually into lymphoblastoid cell lines (LCLs). In these infected B lymphocytes EBV expresses eleven genes one of which is the Epstein-Barr nuclear antigen (EBNA) 3C. This protein is essential for B lymphocyte transformation and there is a mounting body of evidence demonstrating that EBNA3C is linked to cellular and viral transcription. However, the mechanism by which EBNA3C regulates events involved in EBV mediated B lymphocyte transformation is not fully understood. The specific aims of this proposal are: (1) To investigate the roles of EBNA3C in regulating viral and cellular gene expression in EBV transformed primary human B-lymphocytes. (2) To identify cellular proteins interacting with EBNA3C and the critical functional domains interacting with these cellular proteins. (3) To genetically characterize the EBNA3C gene by introduction of specific mutations in the open reading frame and testing for transformation of primary B-lymphocytes and to analyze the properties of the recombinant LCLs transformed by latently infected EBNA3C mutant viruses.